tbuckley/cabot-search huggingface dataset:
ERK1/2 Phosphorylation Predicts Survival in Recurrent Glioblastoma Following Intracerebral and Adjuvant PD-1/CTLA-4 Immunotherapy: A REMARK-guided Analysis
Authors: Víctor A. Arrieta, Johnny Duerinck, Kirsten B. Burdett, Karl J. Habashy, Wietse Geens, Andrew Gould, Julia K. Schwarze, Crismita Dmello, Kwang-Soo Kim, Ruth Saganty, Li Chen, Alberto Moscona, Matthew McCord, Catalina Lee-Chang, Craig M. Horbinski, Hui Zhang, Roger Stupp, Bart Neyns, Adam M. Sonabend
Journal: Clinical Cancer Research (2023)

Evidence suggests that MAPK pathway activation, as measured by ERK1/2 phosphorylation (p-ERK), predicts overall survival (OS) in patients with recurrent glioblastoma receiving anti-PD-1 therapy. We aimed to validate these findings in independent cohorts.
Targeted Radiation Delivery before Haploidentical HCT for High-risk Leukemia or MDS Patients Yields Long-term Survivors
Authors: Johnnie J. Orozco, Phuong T. Vo, Ted A. Gooley, Robyn L. Haaf, Sally J. Lundberg, Donald K. Hamlin, D. Scott Wilbur, Manuela C. Matesan, Darrell R. Fisher, Ajay K. Gopal, Damian J. Green, John M. Pagel, Brenda M. Sandmaier
Journal: Clinical Cancer Research (2023)

Abstract Purpose: Hematopoietic cell transplantation (HCT) has curative potential for myeloid malignancies, though many patients cannot tolerate myeloablative conditioning with high-dose chemotherapy alone or with total-body irradiation (TBI). Here we report long-term outcomes from a phase I/II study using iodine-131 (131I)-anti-CD45 antibody BC8 combined with nonmyeloablative conditioning prior to HLA-haploidentical HCT in adults with high-risk relapsed/ refractory acute myeloid or lymphoid leukemia (AML or ALL), or myelodysplastic syndrome (MDS; ClinicalTrials.gov, NCT00589316). Patients and Methods: Patients received a tracer diagnostic dose before a therapeutic infusion of 131I­anti-CD45 to deliver escalating doses (12–26 Gy) to the dose-limiting organ. Patients subsequently received fludarabine, cyclophosphamide (CY), and 2 Gy TBI conditioning before haploidentical marrow HCT. GVHD prophylaxis was posttransplant CY plus tacrolimus and mycophenolate mofetil. Results: Twenty-five patients (20 with AML, 4 ALL and 1 high-risk MDS) were treated; 8 had ≥ 5% blasts by morphology (range 9%–20%), and 7 had previously failed HCT. All 25 patients achieved a morphologic remission 28 days after HCT, with only 2 patients showing minimal residual disease (0.002–1.8%) by flow cytometry. Median time to engraftment was 15 days for neutrophils and 23 days for platelets. Point estimates for overall survival and progression-free survival were 40% and 32% at 1 year, and 24% at 2 years, respectively. Point estimates of relapse and nonrelapse mortality at 1 year were 56% and 12%, respectively. Conclusions: 131I-anti-CD45 radioimmunotherapy prior to haploidentical HCT is feasible and can be curative in some patients, including those with disease, without additional toxicity.
Olaparib plus Durvalumab, with or without Bevacizumab, as Treatment in PARP Inhibitor-Naïve Platinum-Sensitive Relapsed Ovarian Cancer: A Phase II Multi-Cohort Study
Authors: Yvette Drew, Jae-Weon Kim, Richard T. Penson, David M. O'Malley, Christine Parkinson, Patricia Roxburgh, Ruth Plummer, Seock-Ah Im, Martina Imbimbo, Michelle Ferguson, Ora Rosengarten, Neeltje Steeghs, Min Hwan Kim, Einav Gal-Yam, Daliah Tsoref, Jae-Hoon Kim, Benoit You, Maja De Jonge, Roy Lalisang, Eelke Gort, Sara Bastian, Kassondra Meyer, Laura Feeney, Nigel Baker, Mei-Lin Ah-See, Susan M. Domchek, Susana Banerjee
Journal: Clinical Cancer Research (2023)

Abstract Purpose: Early results from the phase II MEDIOLA study (NCT02734004) in germline BRCA1- and/or BRCA2-mutated (gBRCAm) platinum-sensitive relapsed ovarian cancer (PSROC) showed promising efficacy and safety with olaparib plus durvalumab. We report efficacy and safety of olaparib plus durvalumab in an expansion cohort of women with gBRCAm PSROC (gBRCAm expansion doublet cohort) and two cohorts with non-gBRCAm PSROC, one of which also received bevacizumab (non-gBRCAm doublet and triplet cohorts). Patients and Methods: In this open-label, multicenter study, PARP inhibitor-naïve patients received olaparib plus durvalumab treatment until disease progression; the non-gBRCAm triplet cohort also received bevacizumab. Primary endpoints were objective response rate (ORR; gBRCAm expansion doublet cohort), disease control rate (DCR) at 24 weeks (non-gBRCAm cohorts), and safety (all cohorts). Results: The full analysis and safety analysis sets comprised 51, 32, and 31 patients in the gBRCAm expansion doublet, non-gBRCAm doublet, and non-gBRCAm triplet cohorts, respectively. ORR was 92.2% [95% confidence interval (CI), 81.1–97.8] in the gBRCAm expansion doublet cohort (primary endpoint); DCR at 24 weeks was 28.1% (90% CI, 15.5–43.9) in the non-gBRCAm doublet cohort (primary endpoint) and 74.2% (90% CI, 58.2–86.5) in the non-gBRCAm triplet cohort (primary endpoint). Grade ≥ 3 adverse events were reported in 47.1%, 65.6%, and 61.3% of patients in the gBRCAm expansion doublet, non-gBRCAm doublet, and non-gBRCAm triplet cohorts, respectively, most commonly anemia. Conclusions: Olaparib plus durvalumab continued to show notable clinical activity in women with gBRCAm PSROC. Olaparib plus durvalumab with bevacizumab demonstrated encouraging clinical activity in women with non-gBRCAm PSROC. No new safety signals were identified.
Cross-regulation of antibody responses against the SARS-CoV-2 Spike protein and commensal microbiota via molecular mimicry
Authors: Marina Bondareva, Lisa Budzinski, Pawel Durek, Mario Witkowski, Stefan Angermair, Justus Ninnemann, Jakob Kreye, Philine Letz, Marta Ferreira-Gomes, Iaroslav Semin, Gabriela Maria Guerra, S. Momsen Reincke, Elisa Sánchez-Sendin, Selin Yilmaz, Toni Sempert, Gitta Anne Heinz, Caroline Tizian, Martin Raftery, Günther Schönrich, Daria Matyushkina, Ivan V. Smirnov, Vadim M. Govorun, Eva Schrezenmeier, Anna-Luisa Stefanski, Thomas Dörner, Silvia Zocche, Edoardo Viviano, Nele Klement, Katharina Johanna Sehmsdorf, Alexander Lunin, Hyun-Dong Chang, Marina Drutskaya, Liubov Kozlovskaya, Sascha Treskatsch, Andreas Radbruch, Andreas Diefenbach, Harald Prüss, Philipp Enghard, Mir-Farzin Mashreghi, Andrey A. Kruglov
Journal: Cell Host & Microbe (2023)

The commensal microflora provides a repertoire of antigens that illicit mucosal antibodies. In some cases, these antibodies can cross-react with host proteins, inducing autoimmunity, or with other microbial antigens. We demonstrate that the oral microbiota can induce salivary anti-SARS-CoV-2 Spike IgG antibodies via molecular mimicry. Anti-Spike IgG antibodies in the saliva correlated with enhanced abundance of Streptococcus salivarius 1 month after anti-SARS-CoV-2 vaccination. Several human commensal bacteria, including S. salivarius, were recognized by SARS-CoV-2-neutralizing monoclonal antibodies and induced cross-reactive anti-Spike antibodies in mice, facilitating SARS-CoV-2 clearance. A specific S. salivarius protein, RSSL-01370, contains regions with homology to the Spike receptor-binding domain, and immunization of mice with RSSL-01370 elicited anti-Spike IgG antibodies in the serum. Additionally, oral S. salivarius supplementation enhanced salivary anti-Spike antibodies in vaccinated individuals. Altogether, these data show that distinct species of the human microbiota can express molecular mimics of SARS-CoV-2 Spike protein, potentially enhancing protective immunity.
Joint associations of device-measured physical activity and abdominal obesity with incident cardiovascular disease: a prospective cohort study
Authors: Miguel Adriano Sanchez-Lastra, Ding Ding, Borja Del Pozo Cruz, Knut Eirik Dalene, Carlos Ayán, Ulf Ekelund, Jakob Tarp
Journal: British Journal of Sports Medicine (2023)

Objective To examine the joint associations between physical activity and abdominal obesity with the risk of cardiovascular disease (CVD) events. Methods We included 70 830 UK Biobank participants (mean age±SD=61.6 ± 7.9 years; 56.4% women) with physical activity measured by wrist-worn accelerometers and without major chronic diseases. Participants were jointly categorised into six groups based on their physical activity level (tertiles of total volume and specific intensity levels) and presence or absence of abdominal obesity based on measured waist circumference. Associations with incident CVD (fatal and non-fatal events) were determined using proportional subdistribution hazard models with multivariable adjustment. Results After excluding events during the first 2 years of follow-up, participants were followed for a median of 6.8 years, during which 2795 CVD events were recorded. Compared with the low abdominal adiposity and highest tertile of physical activity, abdominal obesity was associated with higher risk of incident CVD, especially in those with low levels of vigorous-intensity physical activity (HR 1.42, 95% CI 1.22 to 1.64). Approximately 500 min per week of moderate-to-vigorous intensity and approximately 30–35 min of vigorous-intensity physical activity offset the association of abdominal obesity and the risk of having a CVD event. Conclusion Physical activity equivalent to approximately 30–35 min of vigorous intensity per week appears to offset the association between abdominal obesity and incident CVD. About 15 times more physical activity of at least moderate intensity is needed to achieve similar results.
Methodical Manipulation of the TME in Ovarian Cancer
Authors: Pamela Soberanis Pina, Amit M. Oza
Journal: Clinical Cancer Research (2023)

The complex interplay between ovarian cancer cells and the tumor microenvironment (TME) modulates progression, with dynamic cellular interactions influenced by external modulators, including neoadjuvant chemotherapy (NACT). A recent article described the alterations within the TME following NACT, either with or without bevacizumab, in ovarian cancer. See related article by Tavira et al., p. 176.
The SLC6A15–SLC6A20 Neutral Amino Acid Transporter Subfamily: Functions, Diseases, and Their Therapeutic Relevance
Authors: Jędrzej Kukułowicz, Krzysztof Pietrzak-Lichwa, Klaudia Klimończyk, Nathalie Idlin, Marek Bajda
Journal: Pharmacological Reviews (2023)

The neutral amino acid transporter subfamily that consists of six members, consecutively SLC6A15–SLC620, also called orphan transporters, represents membrane, sodium-dependent symporter proteins that belong to the family of solute carrier 6 (SLC6). Primarily, they mediate the transport of neutral amino acids from the extracellular milieu toward cell or storage vesicles utilizing an electric membrane potential as the driving force. Orphan transporters are widely distributed throughout the body, covering many systems; for instance, the central nervous, renal, or intestinal system, supplying cells into molecules used in biochemical, signaling, and building pathways afterward. They are responsible for intestinal absorption and renal reabsorption of amino acids. In the central nervous system, orphan transporters constitute a significant medium for the provision of neurotransmitter precursors. Diseases related with aforementioned transporters highlight their significance; SLC6A19 mutations are associated with metabolic Hartnup disorder, whereas altered expression of SLC6A15 has been associated with a depression/stress-related disorders. Mutations of SLC6A18-SLCA20 cause iminoglycinuria and/or hyperglycinuria. SLC6A18-SLC6A20 to reach the cellular membrane require an ancillary unit ACE2 that is a molecular target for the spike protein of the SARS-CoV-2 virus. SLC6A19 has been proposed as a molecular target for the treatment of metabolic disorders resembling gastric surgery bypass. Inhibition of SLC6A15 appears to have a promising outcome in the treatment of psychiatric disorders. SLC6A19 and SLC6A20 have been suggested as potential targets in the treatment of COVID-19. In this review, we gathered recent advances on orphan transporters, their structure, functions, related disorders, and diseases, and in particular their relevance as therapeutic targets. <h3>Significance Statement</h3> The following review systematizes current knowledge about the SLC6A15-SLCA20 neutral amino acid transporter subfamily and their therapeutic relevance in the treatment of different diseases.
Age at Diagnosis of Atrial Fibrillation and Incident Dementia
Authors: Wenya Zhang, Jie Liang, Chenglong Li, Darui Gao, Qian Ma, Yang Pan, Yongqian Wang, Wuxiang Xie, Fanfan Zheng
Journal: JAMA Network Open (2023)

Importance Epidemiological evidence regarding the association between atrial fibrillation (AF) onset age and risk of incident dementia remains unexplored. Objective To examine whether age at AF diagnosis is associated with risk of incident dementia and its subtypes. Design, Setting, and Participants This prospective, population-based cohort study used data from UK Biobank, a public, open-access database in the UK with baseline information collected from 2006 to 2010. A total of 433 746 participants were included in the main analysis after excluding participants with a diagnosis of dementia or AF at baseline, missing data on covariates, or having dementia before AF onset during a median follow-up of 12.6 years. Data were analyzed from October to December 2022. Exposures AF diagnosis and age at AF diagnosis according to age groups (&amp;amp;lt;65 years, 65-74 years, or ≥75 years). Main Outcomes and Measures Incident dementia, ascertained through linkage from multiple databases until December 31, 2021. Cox proportional hazards models and the propensity score matching method were adopted to estimate the association between AF onset age and incident dementia. Results Of 433 746 included participants, 236 253 (54.5%) were female, the mean (SD) age was 56.9 (8.1) years, and 409 990 (94.5%) were White. Compared with individuals without AF, 30 601 individuals with AF had a higher risk of developing all-cause dementia (adjusted hazard ratio [HR], 1.42; 95% CI, 1.32-1.52) and vascular dementia (VD; adjusted HR, 2.06; 95% CI, 1.80-2.36), but not Alzheimer disease (AD; adjusted HR, 1.08; 95% CI, 0.96-1.21). Among participants with AF, younger age at AF onset was associated with higher risks of developing all-cause dementia (adjusted HR per 10-year decrease, 1.23; 95% CI, 1.16-1.32), AD (adjusted HR per 10-year decrease, 1.27; 95% CI, 1.13-1.42), and VD (adjusted HR per 10-year decrease, 1.35; 95% CI, 1.20-1.51). After propensity score matching, individuals with AF diagnosed before age 65 years had the highest HR of developing all-cause dementia (adjusted HR, 1.82; 95% CI, 1.54-2.15), followed by AF diagnosed at age 65 to 74 years (adjusted HR, 1.47; 95% CI, 1.31-1.65) and diagnosed at age 75 years or older (adjusted HR, 1.11; 95% CI, 0.96-1.28). Similar results can be seen in AD and VD. Conclusions and Relevance In this prospective cohort study, earlier onset of AF was associated with an elevated risk of subsequent all-cause dementia, AD, and VD, highlighting the importance of monitoring cognitive function among patients with AF, especially those younger than 65 years at diagnosis.
Laser Epilation as an Adjunct to Standard Care in Reducing Pilonidal Disease Recurrence in Adolescents and Young Adults
Authors: Peter C. Minneci, Lindsay A. Gil, Jennifer N. Cooper, Lindsey Asti, Leah Nishimura, Carley M. Lutz, Katherine J. Deans
Journal: JAMA Surgery (2023)

Recurrence continues to be a significant challenge in the treatment and management of pilonidal disease.
Estimated Effectiveness of Coadministration of the BNT162b2 BA.4/5 COVID-19 Vaccine With Influenza Vaccine
Authors: Leah J. McGrath, Deepa Malhotra, Amanda C. Miles, Verna L. Welch, Manuela Di Fusco, Andy Surinach, Andrea Barthel, Tamuno Alfred, Luis Jodar, John M. McLaughlin
Journal: JAMA Network Open (2023)

No data comparing the estimated effectiveness of coadministering COVID-19 vaccines with seasonal influenza vaccine (SIV) in the community setting exist.
Reduction of Financial Health Incentives and Changes in Physical Activity
Authors: Sean Spilsbury, Piotr Wilk, Carolyn Taylor, Harry Prapavessis, Marc Mitchell
Journal: JAMA Network Open (2023)

Importance Governments and others continue to use financial incentives to influence citizen health behaviors like physical activity. However, when delivered on a population scale they can be prohibitively costly, suggesting more sustainable models are needed. Objectives To evaluate the association of incomplete financial incentive withdrawal (“schedule thinning”) with physical activity after more than a year of incentive intervention and to explore whether participant characteristics (eg, app engagement and physical activity) are associated with withdrawal outcomes. Design, Setting, and Participants This case-control study with a pre-post quasi-experimental design included users of a government-funded health app focused on financial incentives. Eligible participants were residents in 3 Canadian provinces over 25 weeks in 2018 and 2019. Data were analyzed from July 2021 to December 2022. Exposure Due to fiscal constraints, financial incentives for daily physical activity goals were withdrawn in Ontario in December 2018 (case)—representing a 90% reduction in incentive earnings—but not in British Columbia or Newfoundland and Labrador (controls). Main Outcome and Measures The primary outcome was objectively assessed weekly mean daily step count. Linear regression models were used to compare pre-post changes in daily step counts between provinces (a difference-in-differences approach). Separate models were developed to examine factors associated with changes in daily step count (eg, app engagement and physical activity). Clinically meaningful initial effect sizes were previously reported (approximately 900 steps/d overall and 1800 steps/d among the physically inactive). Results In total there were 584 760 study participants (mean [SD] age, 34.3 [15.5] years; 220 388 women [63.5%]), including 438 731 from Ontario, 124 101 from British Columbia, and 21 928 from Newfoundland and Labrador. Significant physical activity declines were observed when comparing pre-post changes in Ontario to British Columbia (−198 steps/d; 95% CI, −224 to −172 steps/d) and Newfoundland and Labrador (−274 steps/d; 95% CI, −323 to −225 steps/d). The decrease was most pronounced for highly engaged Ontario users (−328 steps/d; 95% CI, −343 to −313 steps/d). Among physically inactive Ontario users, physical activity did not decline following withdrawal (107 steps/d; 95% CI, 90 to 124 steps/d). Conclusions and Relevance In this case-control study of incomplete financial incentive withdrawal, statistically significant daily step count reductions were observed in Ontario; however, these declines were modest and not clinically meaningful. Amidst substantial program savings, the physical activity reductions observed here may be acceptable to decision-makers working within finite budgets.
Pathologist Characteristics Associated With Rendering Higher-Grade Diagnoses for Melanocytic Lesions
Authors: Kathleen F. Kerr, David E. Elder, Michael W. Piepkorn, Stevan R. Knezevich, Megan M. Eguchi, Hannah L. Shucard, Lisa M. Reisch, Joann G. Elmore, Raymond L. Barnhill
Journal: JAMA Dermatology (2023)

The incidence of melanoma diagnoses has been increasing in recent decades, and controlled studies have indicated high histopathologic discordance across the intermediate range of melanocytic lesions. The respective causes for these phenomena remain incompletely understood.
Heat-Related Deaths From CVD Expected to Surge by Midcentury
Authors: Emily Harris
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Daily Exercise May Offset Otherwise Sedentary Lifestyle
Authors: Emily Harris
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
CDC Report: Health Worker Mental Health Crisis Continued in 2022
Authors: Emily Harris
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Skin Cancers in Medicare Beneficiaries With Actinic Keratoses
Authors: Cassandra Mohr, Yao Li, Lucy J. Navsaria, Candice L. Hinkston, Sanjay S. Shete, David J. Margolis, Mackenzie R. Wehner
Journal: JAMA Dermatology (2023)

Actinic keratoses (AK) are common premalignant skin lesions with a small risk of progressing to cutaneous squamous cell carcinoma (SCC). There is some evidence that patients with AKs also have increased risks of other skin cancers beyond SCC. However, the absolute risks of skin cancer in patients with AKs are unknown.